FIGURE 2. Why rewire cell signaling circuits?

a| understanding design principles. Traditionally, methods like gene disruption are used to dissect a signaling network. Synthetic approaches offer complementary information by creating alternative versions of a network that differ both in the network connectivity or in the strength of links. By mapping the space of functional (red circles) vs. nonfunctional (blue circles) variants, one gains a deeper understanding of functional requirements.

b | constructing designer signaling pathways for therapeutic or biotechnology applications. We hope to assemble a toolkit of signaling modules that can be used to create cells with designed signaling responses. An anti-cancer cell might detect a combination of tumor signals, and yield responses such as production of imaging reagents, cell killing, or secretion of factors that disrupt the tumor microenvironment. Such a cell might also have safety switches that could disable the cell if needed. An immunosuppressive cell might detect a combination of auto-immune response or transplant rejection signals, and trigger localized countermeasures, such as secretion of anti-inflammatory cytokines. A smart bioproduction (fermentation) cell would be engineered to precisely modulate the flux in growth versus production pathways in response to the stress state of the cell, thus optimizing overall yield.